Author Manuscript Published OnlineFirst on June 20, 2013; DOI: 10.1158/1078-0432.CCR-12-0781 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Controlled local delivery of CTLA-4 blocking antibody induces CD8+ T cell dependent tumor eradication and decreases risk of toxic side-effects Marieke F. Fransen1, Tetje C. van der Sluis1, Ferry Ossendorp1, Ramon Arens1, Cornelis J. M. Melief1,2 1Department of Immunohematology and Blood Transfusion, Leiden University Medical Hospital, Leiden, the Netherlands. 2ISA Pharmaceuticals, Leiden, the Netherlands. Running title: Low dose CTLA-4 blocking antibody treatment Keywords: Anti tumor immunity, CD8+ T cells, Cytotoxic T-Lymphocyte Antigen-4, slow- release delivery Corresponding author: Cornelis JM Melief, Department of Immunohe- matology and Blood Transfusion, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands. Phone: 31-715263800; Fax: 011-31- 715216751. E-mail:
[email protected] Word count: 3297, 5 Figures. 1 Downloaded from clincancerres.aacrjournals.org on September 30, 2021. © 2013 American Association for Cancer Research. Author Manuscript Published OnlineFirst on June 20, 2013; DOI: 10.1158/1078-0432.CCR-12-0781 Author manuscripts have been peer reviewed and accepted for publication but have not yet been edited. Statement of translational relevance: Systemic delivery of CTLA-4 blocking antibodies induces anti-tumor immune responses in pre-clinical models and patients but dose-limiting toxicity hampers clinical success. We have used a novel delivery system based on the slow-release agent Montanide ISA-51 to distribute CTLA-4 blocking antibody in the lymphoid drainage area of the tumor, which stimulates local but not systemic T cells.